Abstract A major challenge in advancing diabetes research has been the lack of good human models to study genetic variants emerging from genome-wide association studies (GWAS) in complex disease. We desperately need methods to assess more rapidly the function of genetic variants in human models of cell biology, in particular beta-cell biology. In this Catalyst Award project, I will develop a novel model of human beta-cell function, using a fluorescent reporter of insulin secretion that enables single-cell analysis. I will use this system to test the effects of candidate genes associated with type 2 diabetes (T2D). This work will lay the foundation for the development of disease-modifying diabetes therapeutics based on human genetics. This challenge is important for two major reasons. First, the lack of a reliable model for human beta-cell function is a major barrier to diabetes research. Prior to 2011, no human beta cell lines existed. Second, solving this challenge would enable much more rapid translation from genes to function. With this Catalyst Award, I will leverage my expertise in developing high- throughput biological assays to develop a human model of beta-cell function for the rapid study of the effects of T2D variants.